Target Binding Site Detail
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T28887 | Target Info | |||
| Target Name | Histone deacetylase 8 (HDAC8) | ||||
| Synonyms | Histone deacetylase-8; HDACL1; HD8; CDA07 | ||||
| Target Type | Clinical trial Target | ||||
| Gene Name | HDAC8 | ||||
| Biochemical Class | Carbon-nitrogen hydrolase | ||||
| UniProt ID | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | Trichostatin A | Ligand Info | |||
| Canonical SMILES | CC(C=C(C)C=CC(=O)NO)C(=O)C1=CC=C(C=C1)N(C)C | ||||
| InChI | 1S/C17H22N2O3/c1-12(5-10-16(20)18-22)11-13(2)17(21)14-6-8-15(9-7-14)19(3)4/h5-11,13,22H,1-4H3,(H,18,20)/b10-5+,12-11+/t13-/m1/s1 | ||||
| InChIKey | RTKIYFITIVXBLE-QEQCGCAPSA-N | ||||
| PubChem Compound ID | 444732 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 1T64 Crystal Structure of human HDAC8 complexed with Trichostatin A | ||||||
| Method | X-ray diffraction | Resolution | 1.90 Å | Mutation | No | [1] |
| PDB Sequence |
LVPVYIYSPE
23 YVSMCDSLAK33 IPKRASMVHS43 LIEAYALHKQ53 MRIVKPKVAS63 MEEMATFHTD 73 AYLQHLQKVS83 QEGDDDHPDS93 IEYGLGYDCP103 ATEGIFDYAA113 AIGGATITAA 123 QCLIDGMCKV133 AINWSGGWHH143 AKKDEASGFC153 YLNDAVLGIL163 RLRRKFERIL 173 YVDLDLHHGD183 GVEDAFSFTS193 KVMTVSLHKF203 SPGFFPGTGD213 VSDVGLGKGR 223 YYSVNVPIQD233 GIQDEKYYQI243 CESVLKEVYQ253 AFNPKAVVLQ263 LGADTIAGDP 273 MCSFNMTPVG283 IGKCLKYILQ293 WQLATLILGG303 GGYNLANTAR313 CWTYLTGVIL 323 GKTLSSEIPD333 HEFFTAYGPD343 YVLEITPSCR353 PDRNEPHRIQ363 QILNYIKGNL 373 KHVV
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ILE34
3.621
PRO35
3.300
ARG37
3.745
TYR100
3.234
ASP101
3.858
TYR111
3.263
TRP141
3.360
HIS142
2.766
HIS143
2.700
GLY151
3.577
PHE152
3.354
|
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| PDB ID: 3F0R Crystal Structure Analysis of Human HDAC8 complexed with trichostatin A in a new monoclinic crystal form | ||||||
| Method | X-ray diffraction | Resolution | 2.54 Å | Mutation | No | [2] |
| PDB Sequence |
SLVPVYIYSP
22 EYVSMCDSLI34 PKRASMVHSL44 IEAYALHKQM54 RIVKPKVASM64 EEMATFHTDA 74 YLQHLQKVSQ84 EGDDDHPDSI94 EYGLGYDCPA104 TEGIFDYAAA114 IGGATITAAQ 124 CLIDGMCKVA134 INWSGGWHHA144 KKDEASGFCY154 LNDAVLGILR164 LRRKFERILY 174 VDLDLHHGDG184 VEDAFSFTSK194 VMTVSLHKFS204 PGFFPGTGDV214 SDVGLGKGRY 224 YSVNVPIQDG234 IQDEKYYQIC244 ESVLKEVYQA254 FNPKAVVLQL264 GADTIAGDPM 274 CSFNMTPVGI284 GKCLKYILQW294 QLATLILGGG304 GYNLANTARC314 WTYLTGVILG 324 KTLSSEIPDH334 EFFTAYGPDY344 VLEITPSCRP354 DRNEPHRIQQ364 ILNYIKGNLK 374 HVVI
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ILE34
3.467
PRO35
3.351
ARG37
3.238
TYR100
3.328
ASP101
4.067
PRO103
4.498
TYR111
3.281
TRP141
3.369
HIS142
3.234
HIS143
3.090
GLY151
4.007
PHE152
3.318
|
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| PDB ID: 4QA3 Crystal structure of T311M HDAC8 in complex with Trichostatin A (TSA) | ||||||
| Method | X-ray diffraction | Resolution | 2.88 Å | Mutation | Yes | [3] |
| PDB Sequence |
LVPVYIYSPE
23 YVSMCDSLAK33 IPKRASMVHS43 LIEAYALHKQ53 MRIVKPKVAS63 MEEMATFHTD 73 AYLQHLQKVS83 QEGDDDHPDS93 IEYGLGYDCP103 ATEGIFDYAA113 AIGGATITAA 123 QCLIDGMCKV133 AINWSGGWHH143 AKKDEASGFC153 YLNDAVLGIL163 RLRRKFERIL 173 YVDLDLHHGD183 GVEDAFSFTS193 KVMTVSLHKF203 SPGFFPGTGD213 VSDVGLGKGR 223 YYSVNVPIQD233 GIQDEKYYQI243 CESVLKEVYQ253 AFNPKAVVLQ263 LGADTIAGDP 273 MCSFNMTPVG283 IGKCLKYILQ293 WQLATLILGG303 GGYNLANMAR313 CWTYLTGVIL 323 GKTLSSEIPD333 HEFFTAYGPD343 YVLEITPSCR353 PDRNEPHRIQ363 QILNYIKGNL 373 KHVVI
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| PDB ID: 5D1B Crystal structure of G117E HDAC8 in complex with TSA | ||||||
| Method | X-ray diffraction | Resolution | 2.90 Å | Mutation | Yes | [4] |
| PDB Sequence |
LVPVYIYSPE
23 YVSMCDSLAK33 IPKRASMVHS43 LIEAYALHKQ53 MRIVKPKVAS63 MEEMATFHTD 73 AYLQHLQKVS83 QEGEYGLGYD101 CPATEGIFDY111 AAAIGEATIT121 AAQCLIDGMC 131 KVAINWSGGW141 HHAKKDEASG151 FCYLNDAVLG161 ILRLRRKFER171 ILYVDLDLHH 181 GDGVEDAFSF191 TSKVMTVSLH201 KFSPGFFPGT211 GDVSDVGLGK221 GRYYSVNVPI 231 QDGIQDEKYY241 QICESVLKEV251 YQAFNPKAVV261 LQLGADTIAG271 DPMCSFNMTP 281 VGIGKCLKYI291 LQWQLATLIL301 GGGGYNLANT311 ARCWTYLTGV321 ILGKTLSSEI 331 PDHEFFTAYG341 PDYVLEITPS351 CRPDRNEPHR361 IQQILNYIKG371 NLKHVV |
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Structural snapshots of human HDAC8 provide insights into the class I histone deacetylases. Structure. 2004 Jul;12(7):1325-34. | ||||
| REF 2 | Structural studies of human histone deacetylase 8 and its site-specific variants complexed with substrate and inhibitors. Biochemistry. 2008 Dec 23;47(51):13554-63. | ||||
| REF 3 | Compromised structure and function of HDAC8 mutants identified in Cornelia de Lange Syndrome spectrum disorders. ACS Chem Biol. 2014 Sep 19;9(9):2157-64. | ||||
| REF 4 | Biochemical and structural characterization of HDAC8 mutants associated with Cornelia de Lange syndrome spectrum disorders. Biochemistry. 2015 Oct 27;54(42):6501-13. | ||||
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